How Long Until It Works

• Should reduce seizures by 2 weeks

• Should also reduce pain in postherapeutic neuralgia by 2 weeks; some patients respond earlier

• May reduce pain in other neuropathic pain syndromes within a few weeks

• If it is not reducing pain within 6–8 weeks, it may require a dosage increase or it may not work at all

• May reduce anxiety in a variety of disorders within a few weeks

• Not yet clear if it has mood-stabilizing effects in bipolar disorder or antineuralgic actions in chronic neuropathic pain, but some patients may respond and if so, would be expected to show clinical effects starting by 2 weeks although it may take several weeks to months to optimize

If It Works

• The goal of treatment is complete remission of symptoms (e.g., seizures)

• The goal of treatment of chronic neuropathic pain is to reduce symptoms as much as possible, especially in combination with other treatments

• Treatment of chronic neuropathic pain most often reduces but does not eliminate symptoms and is not a cure since symptoms usually recur after medicine stopped

• Continue treatment until all symptoms are gone or until improvement is stable and then continue treating indefinitely as long as improvement persists

If It Doesn’t Work (for neuropathic pain or bipolar disorder)

✽ May only be effective in a subset of bipolar patients, in some patients who fail to respond to other mood stabilizers, or it may not work at all

• Many patients have only a partial response where some symptoms are improved but others persist or continue to wax and wane without stabilization of pain or mood

• Other patients may be nonresponders, sometimes called treatment-resistant or treatment-refractory

• Consider increasing dose, switching to another agent or adding an appropriate augmenting agent

• Consider biofeedback or hypnosis for pain

• Consider the presence of noncompliance and counsel patient

• Switch to another agent with fewer side effects

• Consider evaluation for another diagnosis or for a comorbid condition (e.g., medical illness, substance abuse, etc.)

Best Augmenting Combos for Partial Response or Treatment Resistance

✽ Gabapentin is itself an augmenting agent to numerous other anticonvulsants in treating epilepsy; and to lithium, atypical antipsychotics and other anticonvulsants in the treatment of bipolar disorder

• For postherpetic neuralgia, gabapentin can decrease concomitant opiate use

✽ For neuropathic pain, gabapentin can augment tricyclic antidepressants and SNRIs as well as tiagabine, other anticonvulsants and even opiates if done by experts while carefully monitoring in difficult cases

• For anxiety, gabapentin is a second-line treatment to augment SSRIs, SNRIs, or benzodiazepines

Tests

• None for healthy individuals

• False positive readings with the Ames N-Multistix SG^® dipstick test for urinary protein have been reported when gabapentin was administered with other anticonvulsants

GABAPENTIN: SIDE EFFECTS

How Drug Causes Side Effects

• CNS side effects may be due to excessive blockade of voltage-sensitive calcium channels

Notable Side Effects

✽ Sedation, dizziness, ataxia, fatigue, nystagmus, tremor

• Vomiting, dyspepsia, diarrhea, dry mouth, constipation, weight gain

• Blurred vision

• Peripheral edema

• Additional effects in children under age 12: hostility, emotional lability, hyperkinesia, thought disorder, weight gain

Life-Threatening or Dangerous Side Effects

• Sudden unexplained deaths have occurred in epilepsy (unknown if related to gabapentin use)

• Rare activation of suicidal ideation and behavior (suicidality)

Weight Gain

• Occurs in significant minority

Sedation

• Many experience and/or can be significant in amount

• Dose-related; can be problematic at high doses

• Can wear off with time, but may not wear off at high doses

What to Do About Side Effects

• Wait

• Wait

• Wait

• Take more of the dose at night to reduce daytime sedation

• Lower the dose

• Switch to another agent

Best Augmenting Agents for Side Effects

• Many side effects cannot be improved with an augmenting agent

GABAPENTIN: DOSING AND USE

Usual Dosage Range

• 900–1,800 mg/day in 3 divided doses (immediate-release)

Dosage Forms

• Capsule 100 mg, 300 mg, 400 mg, 800 mg

• Tablet 100 mg, 300 mg, 400 mg, 600 mg, 800 mg

• Tablet extended-release 300 mg, 600 mg

• Liquid 250 mg/5 mL – 470 mL bottle

How to Dose

• Postherpetic neuralgia (immediate-release): 300 mg on day 1; on day 2 increase to 600 mg in 2 doses; on day 3 increase to 900 mg in 3 doses; maximum dose generally 1,800 mg/day in 3 doses

• Postherpetic neuralgia (extended-release): 600 mg in the morning on day 1; on day 4 increase to 600 mg twice daily

• Restless leg syndrome (extended-release): 600 mg once daily at about 5 pm

• Seizures (ages 12 and older): initial 900 mg/day in 3 doses; recommended dose generally 1,800 mg/day in 3 doses; maximum dose generally 3,600 mg/day; time between any 2 doses should usually not exceed 12 hours

• Seizures (under age 13): see Children and Adolescents